Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV)

1993 ◽  
Vol 71 (3-4) ◽  
pp. 270-276 ◽  
Author(s):  
Violet G. Yuen ◽  
Chris Orvig ◽  
Katherine H. Thompson ◽  
John H. McNeill

Decreased cardiac function in streptozotocin-diabetic rats has been used as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis(maltolato)oxovanadium(IV), (BMOV), in improving heart function in streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 ± 0.07 μg/mL (16.8 μM) in CT rats and 0.76 ± 0.05 μg/mL (15.2 μM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 ± 3.0 μg/g (0.37 μmol/g) in CT and 26.4 ± 2.6 μg/g (0.53 μmol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with the glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure development (+dP/dT, and −dP/dT) indicated that BMOV treatment resulted in significant correction of the heart dysfunction associated with streptozotocin-induced diabetes in rat.Key words: bis(maltolato)oxovanadium(IV), vanadium, diabetes, streptozotocin, myocardial dysfunction.

1984 ◽  
Vol 62 (6) ◽  
pp. 617-621 ◽  
Author(s):  
Arun G. Tahiliani ◽  
John H. McNeill

Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.


1986 ◽  
Vol 251 (3) ◽  
pp. H571-H580 ◽  
Author(s):  
B. Rodrigues ◽  
J. H. McNeill

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.


1994 ◽  
Vol 72 (5) ◽  
pp. 447-455 ◽  
Author(s):  
Brian Rodrigues ◽  
Paul F. Grassby ◽  
Mary L. Battell ◽  
Stephanie Y. N. Lee ◽  
John H. McNeill

The incidence of mortality from cardiovascular disease is higher in diabetic patients. The objective of the present investigation was to test die hypothesis that the diabetes-induced depression in cardiac function may be due to hypertriglyceridemia. Hyperlipidemia and a depressed left ventricular developed pressure and rate of increase and decrease of ventricular pressure (±dP/dt) were produced in isolated hearts from rats made diabetic with streptozotocin compared with hearts from control animals. This depressed cardiac performance was successfully prevented by hydralazine treatment (for 3 weeks), which also lowered plasma triglyceride levels and suggested that hyperlipidemia may be important in altering cardiac function in experimental diabetic rats. The beneficial effects of clofibrate, verapamil, prazosin, enalapril, and benazepril administration were then studied in diabetic rats. The treatments (with die exception of enalapril) significantly reduced plasma triglyceride levels but did not prevent die onset of heart dysfunction in chronically diabetic rats. These studies suggest that in the chronically diabetic rat, hypertriglyceridemia may not be as important as previously suggested, in the development of cardiac dysfunction. Since acute dichloroacetate perfusion improves cardiac function in 6 week (but not 24 week) diabetic rats, it appears more likely that improving myocardial glycose utilization is more critical than triglyceride lowering, in preventing cardiac dysfunction in die diabetic rat at this time point.Key words: diabetes, triglycerides, heart function, glucose oxidation.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fangli Zhou ◽  
Mingyan Deng ◽  
Linjun Xie ◽  
Yingkun Guo ◽  
Yan Ren

Abstract Background: Diabetic cardiomyopathy is accompanied by left ventricular diastolic dysfunction. Abnormal glucose metabolism plays an important role in the pathogenesis of diabetic cardiomyopathy. However, it’s still not clear whether the influence of hyperglycemia on LV dysfunction is directly affects cardiomyocytes or is related to impaired myocardial perfusion. In this work, we focus on investigating the association between HbA1c and myocardial dysfunction, and if it is independent of myocardial perfusion reserve. Materials and Methods: 64 type 2 diabetic patients were recruited at the endocrine clinic. They are divided into two group, well blood glucose-controlled group (HbA1c&lt;7) and poor glucose-controlled group (HbA1c≥7) T2DM group, according to their HbA1c level. All of the T2DM patients and age-matched healthy volunteers (normal glucose metabolism group, NGM group) underwent CMR to acquire normal values for myocardial strain and perfusion reserve. Results: Well blood glucose-controlled group owned lower global circumferential PSSR than NGM group (p=0.037). Global circumferential PS (p=0.011), global longitudinal PS (p=0.004), global radial PDSR (p=0.005), circumferential PDSR (p=0.001), longitudinal PDSR (p=0.001), global circumferential PSSR (p=0.049), longitudinal PSSR (p=0.041) were significantly lower in the poor glucose-controlled group compared to the NGM group. In the multivariable linear regression analysis, HbA1c existed in all equations except the global circumferential PSSR equation and p&lt;0.05, and Slope, Max SI and Tpeak did not show dependent association with longitudinal and circumferential strain parameters. Conclusion: In subclinical cardiac dysfunction T2DM patients, diastolic dysfunction is more common, but systolic dysfunction is still exist. Poor blood glucose control which is defined as HbA1c ≥ 7% is an independent risk factor for LV deformation for T2DM patients. Subclinical myocardial dysfunction is not triggered by myocardial perfusion reserve.


Author(s):  
I. Iwanegbe ◽  
M. Suleiman ◽  
A. Jimah

Aims: To investigate the effect of food blends (plantain, soybean and ginger) on the blood glucose, lipid profile and haematological indices on streptozotocin induced diabetic rats. Methodology: A total of 35 rats of mean body weight 219.07 g separated into7 groups (5 per group) where induced by a single intraperitoneal (I.P) injection of streptozotocin (0.1 g dissolved in 5 ml of freshly prepared sodium citrate buffer 0.1 M, pH 4.5) at a dose of 40 mg/kg body weight after fasting for 12 hours and fed with flours/blends. The flours were produced from plant materials for different treatments/blends (blend A=100% unripe plantain, B=80% unripe plantain, 14% soybean, 6% ginger, C=70% unripe plantain, 26% soybean, 4% ginger, D= 60% unripe plantain, 38% soybean, 2% ginger, E= 50% unripe plantain, 50% soybean) and the phytochemicals and minerals content were determined. Blood glucose was determined at 5 days interval for 25 days. Diabetes was confirmed in rats with blood glucose concentrations >200 mg/dl. After 25 days rats were anaesthetized with chloroform vapour and blood samples collected by cardiac puncture for haematology and lipid profile determination. Results: The results showed that unripe plantain, soya beans and ginger in adequate proportion(C=70% unripe plantain, 26% soybean, 4% ginger or D= 60% unripe plantain, 38% soybean, 2% ginger) could help to reduce blood glucose, improve haematological parameters and lipid profile. Significant reduction was observed in the blood glucose level of rats fed blends C and D from 286 to 85 mg/dl and 307 to 90 mg/dl respectively at the end of experiment. These results also demonstrated that the inclusion of ginger at 6% causes rise in blood glucose level. Total cholesterol (TC) increased in all the blends. However, the lowest concentration of TC was observed in blends C and D. The highest packed cell volume (60%) and Haemoglobin (20 g/dl) level observed in rats fed blend C was significantly higher than the normal control fed conventional feeds. The increase in packed cell volume (PCV) (50%) and Hb (17 g/dl) in diabetic rats demonstrated that the formulated blend C was able to raise PCV and Hb above 50% and 17 g/dl (Normal control NC) respectively. Significant increase (P<0.05) in low density lipoprotein cholesterol (LDLc) was also observed in all the blends with blend C having the least (4.0 mg/dl) close to NC (2.0 mg/dl). Conclusion: From the results it is evident that blend C will manage and improve the health status of diabetic patients.


2016 ◽  
Vol 311 (3) ◽  
pp. R466-R477 ◽  
Author(s):  
Trevor Hardigan ◽  
Abdul Yasir ◽  
Mohammed Abdelsaid ◽  
Maha Coucha ◽  
Sally El-Shaffey ◽  
...  

The antihyperglycemic agent linagliptin, a dipeptidyl peptidase-4 (DPP-IV) inhibitor, has been shown to reduce inflammation and improve endothelial cell function. In this study, we hypothesized that DPP-IV inhibition with linagliptin would improve impaired cerebral perfusion in diabetic rats, as well as improve insulin-induced cerebrovascular relaxation and reverse pathological cerebrovascular remodeling. We further postulated that these changes would lead to a subsequent improvement of cognitive function. Male Type-2 diabetic and nondiabetic Goto-Kakizaki rats were treated with linagliptin for 4 wk, and blood glucose and DPP-IV plasma levels were assessed. Cerebral perfusion was assessed after treatment using laser-Doppler imaging, and dose response to insulin (10−13 M–10−6 M) in middle cerebral arteries was tested on a pressurized arteriograph. The impact of DPP-IV inhibition on diabetic cerebrovascular remodeling was assessed over a physiologically relevant pressure range, and changes in short-term hippocampus-dependent learning were observed using a novel object recognition test. Linagliptin lowered DPP-IV activity but did not change blood glucose or insulin levels in diabetes. Insulin-mediated vascular relaxation and cerebral perfusion were improved in the diabetic rats with linagliptin treatment. Indices of diabetic vascular remodeling, such as increased cross-sectional area, media thickness, and wall-to-lumen ratio, were also ameliorated; however, improvements in short-term hippocampal-dependent learning were not observed. The present study provides evidence that linagliptin treatment improves cerebrovascular dysfunction and remodeling in a Type 2 model of diabetes independent of glycemic control. This has important implications in diabetic patients who are predisposed to the development of cerebrovascular complications, such as stroke and cognitive impairment.


Author(s):  
Bonisiwe Mbatha ◽  
Andile Khathi ◽  
Ntethelelo Sibiya ◽  
Irvin Booysen ◽  
Patrick Mangundu ◽  
...  

Despite the success of antidiabetic drugs in alleviation of hyperglycaemia, diabetic complications, including renal dysfunction, continue to be a burden. This raises the need to seek alternative therapies that will alleviate these complications. Accordingly, the aim of this study was to investigate the effects of dioxidovanadium(V) complex cis-[VO2(obz)py] on renal function in diabetic rats. Streptozotocin-induced diabetic rats were treated with cis-[VO2(obz)py] (40 mg·kg–1) twice every third day for five weeks. Diabetic untreated and insulin-treated rats served as the diabetic control and positive control, respectively. Blood glucose concentrations, water intake, urinary output, and mean arterial pressure (MAP) were monitored weekly for five weeks. Rats were then euthanized, and blood and kidney tissues were collected for biochemical analysis. Significant decreases in blood glucose concentrations, MAP, glomerular filtration rate (GFR), and SGLT2 expression, as well as plasma angiotensin and aldosterone concentrations, were observed in the treated groups compared with the diabetic control. The complex also increased urinary glucose concentrations, antioxidant enzymes GPx and SOD concentrations, and decreased MDA concentrations and kidney injury molecule (KIM-1) concentrations. These findings suggest that the anti-hyperglycaemic effects of this vanadium complex may ameliorate kidney dysfunction in diabetes.


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